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The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana

The ability to coordinate carbon (C) and nitrogen (N) metabolism enables plants to regulate development and metabolic responses to different environmental conditions. The regulator(s) or sensor(s) that monitor crosstalk between biosynthetic pathways and ultimately control the flow of C or N through...

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Autores principales: Kang, Jiman, Turano, Frank J., Michael, Todd P., Salomé, Patrice A., McClung, C. Robertson, Chen, Lin, Zhang, Shaowu, Srinivasan, Mandyam V., Raymond, Jason, Blankenship, Robert E., Grubmüller, Helmut, Gitai, Zemer, Shapiro, Lucy, Nudo, Randolph J., Sandri-Goldin, Rozanne M., Lindvall, Olle, McKay, Ron, Sirovich, Lawrence, Benzerara, Karim, Menguy, Nicolas, Guyot, François, Dominici, Christian, Gillet, Philippe, Hanotte, O., Ronin, Y., Agaba, M., Nilsson, P., Gelhaus, A., Horstmann, R., Sugimoto, Y., Kemp, S., Gibson, J., Korol, A., Soller, M., Teale, A., Ding, Chunming, Cantor, Charles R., Nagatsuka, Yasuko, Hara-Yokoyama, Miki, Kasama, Takeshi, Takekoshi, Masataka, Maeda, Fumiko, Ihara, Seiji, Fujiwara, Shigeyoshi, Ohshima, Eriko, Ishii, Kumiko, Kobayashi, Toshihide, Shimizu, Kazufumi, Hirabayashi, Yoshio, Kim, Hyun, Yan, Qi, von Heijne, Gunnar, Caputo, Gregory A., Lennarz, William J., Beard, Brian C., Wilson, Samuel H., Smerdon, Michael J., Frugier, Magali, Giegé, Richard, Schimmel, Paul, Joët, Thierry, Eckstein-Ludwig, Ursula, Morin, Christophe, Krishna, Sanjeev, de Boer, Ernie, Rodriguez, Patrick, Bonte, Edgar, Krijgsveld, Jeroen, Katsantoni, Eleni, Heck, Albert, Grosveld, Frank, Strouboulis, John, Moskovitz, Jackob, Stadtman, Earl R., Das, Sudipto, Dixon, Jack E., Cho, Wonhwa, Kazantsev, Alexei V., Krivenko, Angelika A., Harrington, Daniel J., Carter, Richard J., Holbrook, Stephen R., Adams, Paul D., Pace, Norman R., Xue, Dahai, Shi, Hong, Smith, James D., Chen, Xinguo, Noe, Dennis A., Cedervall, Tommy, Yang, Derek D., Eynon, Elizabeth, Brash, Douglas E., Kashgarian, Michael, Flavell, Richard A., Wolin, Sandra L., Goldhaber-Gordon, Ilana, Early, Michael H., Baker, Tania A., Mao, Jianqiang, Chirala, Subrahmanyam S., Wakil, Salih J., Liang, Xue-hai, Liu, Qing, Michaeli, Shulamit, Jiang, Yong, Doolittle, Russell F., Nguyen, Jack T., Wells, James A., Bodley, Annette L., Chakraborty, Asit K., Xie, Suji, Burri, Christian, Shapiro, Theresa A., Sapra, Rajat, Bagramyan, Karine, Adams, Michael W. W., Kristjuhan, Arnold, Wittschieben, Birgitte Ø., Walker, Jane, Roberts, Douglas, Cairns, Bradley R., Svejstrup, Jesper Q., Ji, Yanhong, Zhang, Jianmin, Lee, Alfred Ian, Cedar, Howard, Bergman, Yehudit, Oganesian, A., Poot, M., Daum, G., Coats, S. A., Wright, M. B., Seifert, R. A., Bowen-Pope, D. F., Jiang, Zhen Y., Zhou, Qiong L., Coleman, Kerri A., Chouinard, My, Boese, Queta, Czech, Michael P., Held, G. A., Grinstein, G., Tu, Y., van Noort, John, van der Heijden, Thijn, de Jager, Martijn, Wyman, Claire, Kanaar, Roland, Dekker, Cees, Pitera, Jed W., Swope, William, Bosques, Carlos J., Imperiali, Barbara, Amaro, Rommie, Tajkhorshid, Emad, Luthey-Schulten, Zaida, Singh-Zocchi, Mukta, Dixit, Sanhita, Ivanov, Vassili, Zocchi, Giovanni, Sigg, Daniel, Bezanilla, Francisco, Stefani, Enrico, Lammerding, Jan, Kazarov, Alexander R., Huang, Hayden, Lee, Richard T., Hemler, Martin E., Farver, Ole, Kroneck, Peter M. H., Zumft, Walter G., Pecht, Israel, Lu, Quan, Hope, Lila Weiqiao, Brasch, Michael, Reinhard, Christoph, Cohen, Stanley N., Ding, Sheng, Wu, Tom Y. H., Brinker, Achim, Peters, Eric C., Hur, Wooyoung, Gray, Nathanael S., Schultz, Peter G.
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Publicado: National Academy of Sciences 2003
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Acceso en línea:https://ncbi.nlm.nih.gov/pmc/articles/PMC164539/
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spelling pubmed-1645392003-11-28 The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana Kang, Jiman Turano, Frank J. Proc Natl Acad Sci U S A Biological Sciences The ability to coordinate carbon (C) and nitrogen (N) metabolism enables plants to regulate development and metabolic responses to different environmental conditions. The regulator(s) or sensor(s) that monitor crosstalk between biosynthetic pathways and ultimately control the flow of C or N through them have remained elusive. We used an antisense strategy to demonstrate that the putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of C and N metabolism in Arabidopsis. Seeds from AtGLR1.1-deficient Arabidopsis (antiAtGLR1.1) lines did not germinate in the presence of an animal ionotropic glutamate receptor (iGLR) antagonist, but germination was restored upon coincubation with an iGLR agonist or the putative ligand glutamate. In antiAtGLR1.1 lines, endogenous abscisic acid (ABA) concentrations increased with iGLR antagonist treatments and decreased with coincubation with an iGLR agonist, suggesting that germination was controlled by ABA. antiAtGLR1.1 seedlings also exhibited sensitivity to increased levels of Ca(2+) compared with wild type, and they exhibited a conditional phenotype that was sensitive to the C:N ratio. In the presence of C, specifically sucrose, but not glucose, mannitol, or sorbitol, antiAtGLR1.1 seeds did not germinate, but germination was restored upon coincubation with [Formula: see text] , but not [Formula: see text]. Immunoblot, isoenzyme, and RT-PCR analyses indicate that AtGLR1.1 regulates the accumulation of distinct C- and N-metabolic enzymes, hexokinase 1 (HXK1) and zeaxanthin epoxidase (ABA1), by transcriptional control. We provide a model to describe the role of AtGLR1.1 in C/N metabolism and ABA biosynthesis, which in turn controls seed germination. National Academy of Sciences 2003-05-27 2003-05-08 /pmc/articles/PMC164539/ /pubmed/12738881 http://dx.doi.org/10.1073/pnas.1030961100 Text en Copyright © 2003, The National Academy of Sciences
institution US National Library of Medicine
collection PubMed Central
language English
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format Article
topic Biological Sciences
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spellingShingle Biological Sciences
Biological Sciences
Biological Sciences
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Physical Sciences
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Kang, Jiman
Turano, Frank J.
Michael, Todd P.
Salomé, Patrice A.
McClung, C. Robertson
Chen, Lin
Zhang, Shaowu
Srinivasan, Mandyam V.
Raymond, Jason
Blankenship, Robert E.
Grubmüller, Helmut
Gitai, Zemer
Shapiro, Lucy
Nudo, Randolph J.
Sandri-Goldin, Rozanne M.
Lindvall, Olle
McKay, Ron
Sirovich, Lawrence
Benzerara, Karim
Menguy, Nicolas
Guyot, François
Dominici, Christian
Gillet, Philippe
Hanotte, O.
Ronin, Y.
Agaba, M.
Nilsson, P.
Gelhaus, A.
Horstmann, R.
Sugimoto, Y.
Kemp, S.
Gibson, J.
Korol, A.
Soller, M.
Teale, A.
Ding, Chunming
Cantor, Charles R.
Nagatsuka, Yasuko
Hara-Yokoyama, Miki
Kasama, Takeshi
Takekoshi, Masataka
Maeda, Fumiko
Ihara, Seiji
Fujiwara, Shigeyoshi
Ohshima, Eriko
Ishii, Kumiko
Kobayashi, Toshihide
Shimizu, Kazufumi
Hirabayashi, Yoshio
Kim, Hyun
Yan, Qi
von Heijne, Gunnar
Caputo, Gregory A.
Lennarz, William J.
Beard, Brian C.
Wilson, Samuel H.
Smerdon, Michael J.
Frugier, Magali
Giegé, Richard
Schimmel, Paul
Joët, Thierry
Eckstein-Ludwig, Ursula
Morin, Christophe
Krishna, Sanjeev
de Boer, Ernie
Rodriguez, Patrick
Bonte, Edgar
Krijgsveld, Jeroen
Katsantoni, Eleni
Heck, Albert
Grosveld, Frank
Strouboulis, John
Moskovitz, Jackob
Stadtman, Earl R.
Das, Sudipto
Dixon, Jack E.
Cho, Wonhwa
Kazantsev, Alexei V.
Krivenko, Angelika A.
Harrington, Daniel J.
Carter, Richard J.
Holbrook, Stephen R.
Adams, Paul D.
Pace, Norman R.
Xue, Dahai
Shi, Hong
Smith, James D.
Chen, Xinguo
Noe, Dennis A.
Cedervall, Tommy
Yang, Derek D.
Eynon, Elizabeth
Brash, Douglas E.
Kashgarian, Michael
Flavell, Richard A.
Wolin, Sandra L.
Goldhaber-Gordon, Ilana
Early, Michael H.
Baker, Tania A.
Mao, Jianqiang
Chirala, Subrahmanyam S.
Wakil, Salih J.
Liang, Xue-hai
Liu, Qing
Michaeli, Shulamit
Jiang, Yong
Doolittle, Russell F.
Nguyen, Jack T.
Wells, James A.
Bodley, Annette L.
Chakraborty, Asit K.
Xie, Suji
Burri, Christian
Shapiro, Theresa A.
Sapra, Rajat
Bagramyan, Karine
Adams, Michael W. W.
Kristjuhan, Arnold
Wittschieben, Birgitte Ø.
Walker, Jane
Roberts, Douglas
Cairns, Bradley R.
Svejstrup, Jesper Q.
Ji, Yanhong
Zhang, Jianmin
Lee, Alfred Ian
Cedar, Howard
Bergman, Yehudit
Oganesian, A.
Poot, M.
Daum, G.
Coats, S. A.
Wright, M. B.
Seifert, R. A.
Bowen-Pope, D. F.
Jiang, Zhen Y.
Zhou, Qiong L.
Coleman, Kerri A.
Chouinard, My
Boese, Queta
Czech, Michael P.
Held, G. A.
Grinstein, G.
Tu, Y.
van Noort, John
van der Heijden, Thijn
de Jager, Martijn
Wyman, Claire
Kanaar, Roland
Dekker, Cees
Pitera, Jed W.
Swope, William
Bosques, Carlos J.
Imperiali, Barbara
Amaro, Rommie
Tajkhorshid, Emad
Luthey-Schulten, Zaida
Singh-Zocchi, Mukta
Dixit, Sanhita
Ivanov, Vassili
Zocchi, Giovanni
Sigg, Daniel
Bezanilla, Francisco
Stefani, Enrico
Lammerding, Jan
Kazarov, Alexander R.
Huang, Hayden
Lee, Richard T.
Hemler, Martin E.
Farver, Ole
Kroneck, Peter M. H.
Zumft, Walter G.
Pecht, Israel
Lu, Quan
Hope, Lila Weiqiao
Brasch, Michael
Reinhard, Christoph
Cohen, Stanley N.
Ding, Sheng
Wu, Tom Y. H.
Brinker, Achim
Peters, Eric C.
Hur, Wooyoung
Gray, Nathanael S.
Schultz, Peter G.
The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana
description The ability to coordinate carbon (C) and nitrogen (N) metabolism enables plants to regulate development and metabolic responses to different environmental conditions. The regulator(s) or sensor(s) that monitor crosstalk between biosynthetic pathways and ultimately control the flow of C or N through them have remained elusive. We used an antisense strategy to demonstrate that the putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of C and N metabolism in Arabidopsis. Seeds from AtGLR1.1-deficient Arabidopsis (antiAtGLR1.1) lines did not germinate in the presence of an animal ionotropic glutamate receptor (iGLR) antagonist, but germination was restored upon coincubation with an iGLR agonist or the putative ligand glutamate. In antiAtGLR1.1 lines, endogenous abscisic acid (ABA) concentrations increased with iGLR antagonist treatments and decreased with coincubation with an iGLR agonist, suggesting that germination was controlled by ABA. antiAtGLR1.1 seedlings also exhibited sensitivity to increased levels of Ca(2+) compared with wild type, and they exhibited a conditional phenotype that was sensitive to the C:N ratio. In the presence of C, specifically sucrose, but not glucose, mannitol, or sorbitol, antiAtGLR1.1 seeds did not germinate, but germination was restored upon coincubation with [Formula: see text] , but not [Formula: see text]. Immunoblot, isoenzyme, and RT-PCR analyses indicate that AtGLR1.1 regulates the accumulation of distinct C- and N-metabolic enzymes, hexokinase 1 (HXK1) and zeaxanthin epoxidase (ABA1), by transcriptional control. We provide a model to describe the role of AtGLR1.1 in C/N metabolism and ABA biosynthesis, which in turn controls seed germination.
author Kang, Jiman
Turano, Frank J.
Michael, Todd P.
Salomé, Patrice A.
McClung, C. Robertson
Chen, Lin
Zhang, Shaowu
Srinivasan, Mandyam V.
Raymond, Jason
Blankenship, Robert E.
Grubmüller, Helmut
Gitai, Zemer
Shapiro, Lucy
Nudo, Randolph J.
Sandri-Goldin, Rozanne M.
Lindvall, Olle
McKay, Ron
Sirovich, Lawrence
Benzerara, Karim
Menguy, Nicolas
Guyot, François
Dominici, Christian
Gillet, Philippe
Hanotte, O.
Ronin, Y.
Agaba, M.
Nilsson, P.
Gelhaus, A.
Horstmann, R.
Sugimoto, Y.
Kemp, S.
Gibson, J.
Korol, A.
Soller, M.
Teale, A.
Ding, Chunming
Cantor, Charles R.
Nagatsuka, Yasuko
Hara-Yokoyama, Miki
Kasama, Takeshi
Takekoshi, Masataka
Maeda, Fumiko
Ihara, Seiji
Fujiwara, Shigeyoshi
Ohshima, Eriko
Ishii, Kumiko
Kobayashi, Toshihide
Shimizu, Kazufumi
Hirabayashi, Yoshio
Kim, Hyun
Yan, Qi
von Heijne, Gunnar
Caputo, Gregory A.
Lennarz, William J.
Beard, Brian C.
Wilson, Samuel H.
Smerdon, Michael J.
Frugier, Magali
Giegé, Richard
Schimmel, Paul
Joët, Thierry
Eckstein-Ludwig, Ursula
Morin, Christophe
Krishna, Sanjeev
de Boer, Ernie
Rodriguez, Patrick
Bonte, Edgar
Krijgsveld, Jeroen
Katsantoni, Eleni
Heck, Albert
Grosveld, Frank
Strouboulis, John
Moskovitz, Jackob
Stadtman, Earl R.
Das, Sudipto
Dixon, Jack E.
Cho, Wonhwa
Kazantsev, Alexei V.
Krivenko, Angelika A.
Harrington, Daniel J.
Carter, Richard J.
Holbrook, Stephen R.
Adams, Paul D.
Pace, Norman R.
Xue, Dahai
Shi, Hong
Smith, James D.
Chen, Xinguo
Noe, Dennis A.
Cedervall, Tommy
Yang, Derek D.
Eynon, Elizabeth
Brash, Douglas E.
Kashgarian, Michael
Flavell, Richard A.
Wolin, Sandra L.
Goldhaber-Gordon, Ilana
Early, Michael H.
Baker, Tania A.
Mao, Jianqiang
Chirala, Subrahmanyam S.
Wakil, Salih J.
Liang, Xue-hai
Liu, Qing
Michaeli, Shulamit
Jiang, Yong
Doolittle, Russell F.
Nguyen, Jack T.
Wells, James A.
Bodley, Annette L.
Chakraborty, Asit K.
Xie, Suji
Burri, Christian
Shapiro, Theresa A.
Sapra, Rajat
Bagramyan, Karine
Adams, Michael W. W.
Kristjuhan, Arnold
Wittschieben, Birgitte Ø.
Walker, Jane
Roberts, Douglas
Cairns, Bradley R.
Svejstrup, Jesper Q.
Ji, Yanhong
Zhang, Jianmin
Lee, Alfred Ian
Cedar, Howard
Bergman, Yehudit
Oganesian, A.
Poot, M.
Daum, G.
Coats, S. A.
Wright, M. B.
Seifert, R. A.
Bowen-Pope, D. F.
Jiang, Zhen Y.
Zhou, Qiong L.
Coleman, Kerri A.
Chouinard, My
Boese, Queta
Czech, Michael P.
Held, G. A.
Grinstein, G.
Tu, Y.
van Noort, John
van der Heijden, Thijn
de Jager, Martijn
Wyman, Claire
Kanaar, Roland
Dekker, Cees
Pitera, Jed W.
Swope, William
Bosques, Carlos J.
Imperiali, Barbara
Amaro, Rommie
Tajkhorshid, Emad
Luthey-Schulten, Zaida
Singh-Zocchi, Mukta
Dixit, Sanhita
Ivanov, Vassili
Zocchi, Giovanni
Sigg, Daniel
Bezanilla, Francisco
Stefani, Enrico
Lammerding, Jan
Kazarov, Alexander R.
Huang, Hayden
Lee, Richard T.
Hemler, Martin E.
Farver, Ole
Kroneck, Peter M. H.
Zumft, Walter G.
Pecht, Israel
Lu, Quan
Hope, Lila Weiqiao
Brasch, Michael
Reinhard, Christoph
Cohen, Stanley N.
Ding, Sheng
Wu, Tom Y. H.
Brinker, Achim
Peters, Eric C.
Hur, Wooyoung
Gray, Nathanael S.
Schultz, Peter G.
author_facet Kang, Jiman
Turano, Frank J.
Michael, Todd P.
Salomé, Patrice A.
McClung, C. Robertson
Chen, Lin
Zhang, Shaowu
Srinivasan, Mandyam V.
Raymond, Jason
Blankenship, Robert E.
Grubmüller, Helmut
Gitai, Zemer
Shapiro, Lucy
Nudo, Randolph J.
Sandri-Goldin, Rozanne M.
Lindvall, Olle
McKay, Ron
Sirovich, Lawrence
Benzerara, Karim
Menguy, Nicolas
Guyot, François
Dominici, Christian
Gillet, Philippe
Hanotte, O.
Ronin, Y.
Agaba, M.
Nilsson, P.
Gelhaus, A.
Horstmann, R.
Sugimoto, Y.
Kemp, S.
Gibson, J.
Korol, A.
Soller, M.
Teale, A.
Ding, Chunming
Cantor, Charles R.
Nagatsuka, Yasuko
Hara-Yokoyama, Miki
Kasama, Takeshi
Takekoshi, Masataka
Maeda, Fumiko
Ihara, Seiji
Fujiwara, Shigeyoshi
Ohshima, Eriko
Ishii, Kumiko
Kobayashi, Toshihide
Shimizu, Kazufumi
Hirabayashi, Yoshio
Kim, Hyun
Yan, Qi
von Heijne, Gunnar
Caputo, Gregory A.
Lennarz, William J.
Beard, Brian C.
Wilson, Samuel H.
Smerdon, Michael J.
Frugier, Magali
Giegé, Richard
Schimmel, Paul
Joët, Thierry
Eckstein-Ludwig, Ursula
Morin, Christophe
Krishna, Sanjeev
de Boer, Ernie
Rodriguez, Patrick
Bonte, Edgar
Krijgsveld, Jeroen
Katsantoni, Eleni
Heck, Albert
Grosveld, Frank
Strouboulis, John
Moskovitz, Jackob
Stadtman, Earl R.
Das, Sudipto
Dixon, Jack E.
Cho, Wonhwa
Kazantsev, Alexei V.
Krivenko, Angelika A.
Harrington, Daniel J.
Carter, Richard J.
Holbrook, Stephen R.
Adams, Paul D.
Pace, Norman R.
Xue, Dahai
Shi, Hong
Smith, James D.
Chen, Xinguo
Noe, Dennis A.
Cedervall, Tommy
Yang, Derek D.
Eynon, Elizabeth
Brash, Douglas E.
Kashgarian, Michael
Flavell, Richard A.
Wolin, Sandra L.
Goldhaber-Gordon, Ilana
Early, Michael H.
Baker, Tania A.
Mao, Jianqiang
Chirala, Subrahmanyam S.
Wakil, Salih J.
Liang, Xue-hai
Liu, Qing
Michaeli, Shulamit
Jiang, Yong
Doolittle, Russell F.
Nguyen, Jack T.
Wells, James A.
Bodley, Annette L.
Chakraborty, Asit K.
Xie, Suji
Burri, Christian
Shapiro, Theresa A.
Sapra, Rajat
Bagramyan, Karine
Adams, Michael W. W.
Kristjuhan, Arnold
Wittschieben, Birgitte Ø.
Walker, Jane
Roberts, Douglas
Cairns, Bradley R.
Svejstrup, Jesper Q.
Ji, Yanhong
Zhang, Jianmin
Lee, Alfred Ian
Cedar, Howard
Bergman, Yehudit
Oganesian, A.
Poot, M.
Daum, G.
Coats, S. A.
Wright, M. B.
Seifert, R. A.
Bowen-Pope, D. F.
Jiang, Zhen Y.
Zhou, Qiong L.
Coleman, Kerri A.
Chouinard, My
Boese, Queta
Czech, Michael P.
Held, G. A.
Grinstein, G.
Tu, Y.
van Noort, John
van der Heijden, Thijn
de Jager, Martijn
Wyman, Claire
Kanaar, Roland
Dekker, Cees
Pitera, Jed W.
Swope, William
Bosques, Carlos J.
Imperiali, Barbara
Amaro, Rommie
Tajkhorshid, Emad
Luthey-Schulten, Zaida
Singh-Zocchi, Mukta
Dixit, Sanhita
Ivanov, Vassili
Zocchi, Giovanni
Sigg, Daniel
Bezanilla, Francisco
Stefani, Enrico
Lammerding, Jan
Kazarov, Alexander R.
Huang, Hayden
Lee, Richard T.
Hemler, Martin E.
Farver, Ole
Kroneck, Peter M. H.
Zumft, Walter G.
Pecht, Israel
Lu, Quan
Hope, Lila Weiqiao
Brasch, Michael
Reinhard, Christoph
Cohen, Stanley N.
Ding, Sheng
Wu, Tom Y. H.
Brinker, Achim
Peters, Eric C.
Hur, Wooyoung
Gray, Nathanael S.
Schultz, Peter G.
author_sort Kang, Jiman
title The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana
title_short The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana
title_full The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana
title_fullStr The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana
title_full_unstemmed The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana
title_sort putative glutamate receptor 1.1 (atglr1.1) functions as a regulator of carbon and nitrogen metabolism in arabidopsis thaliana
publisher National Academy of Sciences
publisher_facet National Academy of Sciences
publishDate 2003
url https://ncbi.nlm.nih.gov/pmc/articles/PMC164539/
https://ncbi.nlm.nih.gov/pubmed/12738881
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